ArticlebioRxiv : the preprint server for biology2025
Dynamic PD-L1 Regulation Shapes Tumor Immune Escape and Response to Immunotherapy.
Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
A major challenge in cancer treatment is the ability of tumor cells to adapt to immunotherapy through immune escape, often mediated by the PD-1/PD-L1 pathway. To investigate this, we adapted an ordinary differential equation model of combination therapy, incorporating the dynamics of the immune checkpoint inhibitor Avelumab and the immunostimulant NHS-muIL12. Using literature-derived parameter values from a previous study, we refitted a single parameter across therapies, which showed that PD-L1 expression increased with immunotherapy, while Avelumab blocked its functional signaling, preventing PD-L1 from suppressing T-cell activity. Incorporating therapy-dependent, dynamically regulated PD-L1 expression enabled a biologically grounded mechanism to reproduce experimental observations, leading us to formulate PD-L1 tumor expression as a dynamic variable (
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